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J Ethnopharmacol ; 283: 114701, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34606948


ETHNOPHARMACOLOGICAL RELEVANCE: Xuanfei Baidu Decoction (XFBD), one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, plays an important role in the treatment of mild and/or common patients with dampness-toxin obstructing lung syndrome. AIM OF THE STUDY: The present work aims to elucidate the protective effects and the possible mechanism of XFBD against the acute inflammation and pulmonary fibrosis. METHODS: We use TGF-ß1 induced fibroblast activation model and LPS/IL-4 induced macrophage inflammation model as in vitro cell models. The mice model of lung fibrosis was induced by BLM via endotracheal drip, and then XFBD (4.6 g/kg, 9.2 g/kg) were administered orally respectively. The efficacy and molecular mechanisms in the presence or absence of XFBD were investigated. RESULTS: The results proved that XFBD can effectively inhibit fibroblast collagen deposition, down-regulate the level of α-SMA and inhibit the migration of fibroblasts. IL-4 induced macrophage polarization was also inhibited and the secretions of the inflammatory factors including IL6, iNOS were down-regulated. In vivo experiments, the results proved that XFBD improved the weight loss and survival rate of the mice. The XFBD high-dose administration group had a significant effect in inhibiting collagen deposition and the expression of α-SMA in the lungs of mice. XFBD can reduce bleomycin-induced pulmonary fibrosis by inhibiting IL-6/STAT3 activation and related macrophage infiltration. CONCLUSIONS: Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway.

COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , SARS-CoV-2 , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Fitoterapia , Fibrose Pulmonar/patologia , Fibrose Pulmonar/prevenção & controle , Células RAW 264.7 , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
Phytother Res ; 35(10): 5883-5898, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34427348


Efficient therapy of idiopathic pulmonary fibrosis (IPF) is still a major challenge. The current studies with single-target drug therapy are the pessimistic approaches due to the complex characteristics of IPF. Here, a combination therapy of Tanshinone IIA and Puerarin for IPF was proposed to alleviate IPF due to their antiinflammatory and anti-fibrotic effects. In vivo, the combination therapy could significantly attenuate the area of ground glass opacification that was presented by 85% percentile density score of the micro-CT images when compared to single conditions. In addition, the combination therapy enormously improved the survival rate and alleviated pathological changes in bleomycin (BLM)-induced IPF mice. By using a wide spectrum of infiltration biomarkers in immunofluorescence assay in pathological sections, we demonstrate that fewer IL6 related macrophage infiltration and fibrosis area after this combination therapy, and further proved that IL6-JAK2-STAT3/STAT1 is the key mechanism of the combination therapy. In vitro, combination therapy markedly inhibited the fibroblasts activation and migration which was induced by TGF-ß1 or/and IL6 through JAK2-STAT3/STAT1 signaling pathway. This study demonstrated that combination therapeutic effect of TanIIA and Pue on IPF may be related to the reduced inflammatory response targeting IL6, which could be an optimistic and effective approach for IPF.

Interleucina-6 , Fibrose Pulmonar , Abietanos , Animais , Bleomicina , Fibroblastos/metabolismo , Interleucina-6/metabolismo , Isoflavonas , Pulmão/metabolismo , Camundongos , Fibrose Pulmonar/tratamento farmacológico , Fator de Transcrição STAT1 , Transdução de Sinais
Front Immunol ; 12: 613907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679754


Idiopathic pulmonary fibrosis (IPF) is serious chronic lung disease with limited therapeutic approaches. Inflammation and immune disorders are considered as the main factors in the initiation and development of pulmonary fibrosis. Inspired by the key roles of macrophages during the processes of inflammation and immune disorders, here, we report a new method for direct drug delivery into the in-situ fibrotic tissue sites in vitro and in vivo. First, liposomes containing dexamethasone (Dex-L) are prepared and designed to entry into the macrophages in the early hours, forming the macrophages loaded Dex-L delivery system (Dex-L-MV). Chemokine and cytokine factors such as IL-6, IL-10, Arg-1 are measured to show the effect of Dex-L to the various subtypes of macrophages. Next, we mimic the inflammatory and anti-inflammatory microenvironment by co-culture of polarized/inactive macrophage and fibroblast cells to show the acute inflammation response of Dex-L-MV. Further, we confirm the targeted delivery of Dex-L-MV into the inflammatory sites in vivo, and surprisingly found that injected macrophage containing Dex can reduce the level of macrophage infiltration and expression of the markers of collagen deposition during the fibrotic stage, while causing little systematic toxicity. These data demonstrated the suitability and immune regulation effect of Dex-L-MV for the anti-pulmonary process. It is envisaged that these findings are a step forward toward endogenous immune targeting systems as a tool for clinical drug delivery.

Microambiente Celular/efeitos dos fármacos , Microambiente Celular/imunologia , Dexametasona/administração & dosagem , Imunossupressores/administração & dosagem , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Animais , Biomarcadores , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/etiologia , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Lipossomos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Camundongos , Células NIH 3T3 , Células RAW 264.7
J Agric Food Chem ; 65(30): 6100-6113, 2017 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-28700828


Berberine is a natural herbicidal alkaloid from Coptis chinensis Franch. Here we characterized its herbicidal spectrum and absorption and transportation in the plant, along with the possible mechanism. Berberine showed no effect on the germination of the 10 tested plants. The IC50 values of berberine on the primary root length and fresh weight of the 10 tested plants ranged from 2.91 to 9.79 mg L-1 and 5.76 to 35.07 mg L-1, respectively. Berberine showed a similar herbicidal effect on Bidens pilosa as the commercial naturally derived herbicide cinmethylin. HPLC and fluorescence analysis revealed that berberine was mainly absorbed by B. pilosa root and transported through vascular bundle acropetally. Enzyme activity studies, GC-MS analysis, and SEM and TEM observations indicated that berberine might first function on the cell membrane indicated by variation of the IUFA percent and then cause POD, PPO, and SOD activity changes and cellular structure deformity, which was eventually expressed as the decrease of cell adaptation ability and abnormal cell function and may even result in cell death. Environmental safety evaluation tests revealed that berberine was low in toxicity to Brachydanio rerio. These indicate that berberine has the potential to be a bioherbicide and/or a lead molecule for new herbicides.

Berberina/metabolismo , Berberina/farmacologia , Bidens/metabolismo , Coptis/química , Herbicidas/metabolismo , Herbicidas/farmacologia , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Bidens/efeitos dos fármacos , Transporte Biológico , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo